Endocannabinoids regulate adipokine production and the immune balance of omental adipose tissue in human obesity.

OBJECTIVES: (1) To investigate whether modulation of the cannabinoid type 1 receptor (CB1R) directly regulates the production of adiponectin (ApN) and other adipokines in omental adipose tissue (OAT) of obese subjects, (2) to establish in which cellular fraction of OAT the effects of CB1R blockade take place and (3) to unravel the underlying mechanisms. SUBJECTS AND METHODS: OAT was obtained from 30 obese subjects (body mass index: 40.6±1.3 kg m(-2)) undergoing abdominal surgery. Primary cultures of explants or of freshly isolated adipocytes or stromal-vascular cells (SVCs) were used. RESULTS: In OAT explants, the CB1R blocker Rimonabant upregulated ApN gene expression. mRNA abundance of omentin that exhibits insulin-sensitizing properties was upregulated as well. Conversely, mRNA levels of two pro-inflammatory cytokines, macrophage inflammatory protein (MIP)-1ß and interleukin (IL)-7 were downregulated. We next examined where these effects took place within OAT. CB1R expression was similar in both cellular fractions. In isolated mature adipocytes, blockade of CB1R reproduced the increase of ApN mRNA and the decrease of IL-7 mRNA, while inducing a rise of ApN secretion into the medium. In isolated SVC, gene expression of omentin, which is restricted to this fraction, was augmented, while that of MIP-1ß was diminished. Finally, we deciphered the mechanisms leading to ApN regulation by the endocannabinoid system (ES). We first established that ApN regulation was actually mediated by the CB1R: ApN gene expression was upregulated by Rimonabant and downregulated by the CB1R agonist arachidonyl-2-chloroethylamide (ACEA). Upregulation of ApN by Rimonabant was unaltered by inhibiting cAMP production. However, downregulation of ApN by ACEA was fully reversed by an inhibitor of p38 mitogen-activated protein kinase (p38MAPK) and ACEA increased p38MAPK phosphorylation. CONCLUSIONS: Blockade of CB1R attenuates the inflammatory state in both cellular fractions of OAT either by increasing ApN and omentin production or by decreasing mRNAs of MIP-1ß and IL-7. ApN regulation by the ES partly involves p38MAPK.

Multihormonal control of ob gene expression and leptin secretion from cultured human visceral adipose tissue: increased responsiveness to glucocorticoids in obesity.

The direct role of hormones on leptin synthesis has not yet been studied in cultured adipose cells or tissue from lean and obese subjects. Moreover, this hormonal regulation has never been addressed in human visceral fat, although this site plays a determinant role in obesity-linked disorders. In this study, we investigated the hormonal control of ob expression and leptin production in cultured visceral adipose tissue from lean and obese subjects. We more particularly focused on the interactions between glucocorticoids and insulin. We also briefly tackled the role of cAMP, which is still unknown in man. Visceral (and subcutaneous) adipose tissues from eight obese (body mass index, 41 +/- 2 kg/m2) and nine nonobese (24 +/- 1 kg/m2) subjects were sampled during elective abdominal surgery, and explants were cultured for up to 48 h in MEM. The addition of dexamethasone to the medium increased ob gene expression and leptin secretion in a time-dependent manner. Forty-eight hours after dexamethasone (50 nmol/L) addition, the cumulative integrated ob messenger ribonucleic acid (mRNA) and leptin responses were, respectively, approximately 5- and 4-fold higher in obese than in lean subjects. These responses closely correlated with the body mass index. The stimulatory effect of the glucocorticoid was also concentration dependent (EC50 = approximately 10 nmol/L). Although the maximal response was higher in obese than in lean subjects, the EC50 values were roughly similar in both groups. Unlike dexamethasone, insulin had no direct stimulatory effect on ob gene expression and leptin secretion. Singularly, insulin even inhibited the dexamethasone-induced rise in ob mRNA and leptin release. This inhibition was observed in both lean and obese subjects, whereas the expected stimulation of insulin on glucose metabolism and the accumulation of mRNA species for the insulin-sensitive transporter GLUT4 and glyceraldehyde-3-phosphate dehydrogenase occurred in lean patients only. This inhibitory effect was already detectable at 10 nmol/L insulin and was also observed in subcutaneous fat. Although a lowering of intracellular cAMP concentrations is involved in some of the effects of insulin on adipose tissue, this cannot account for the present finding, because the addition of cAMP to the medium also decreased ob mRNA and leptin secretion (regardless of whether dexamethasone was present). In conclusion, glucocorticoids, at physiological concentrations, stimulated leptin secretion by enhancing the pretranslational machinery in human visceral fat. This effect was more pronounced in obese subjects due to a greater responsiveness of the ob gene and could contribute to the metabolic abnormalities associated with central obesity by para/endocrine actions of hyperleptinemia on adipocytes and liver. Unlike dexamethasone, insulin had no direct stimulatory effect on ob gene expression and leptin secretion, and even prevented the positive response to dexamethasone by a cAMP-independent mechanism that remained functional despite insulin resistance.

Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines.

Plasma levels of type 1 plasminogen activator inhibitor (PAI-1), a risk factor for cardiovascular disease, are elevated in obese subjects, especially those with omental fat accumulation. We investigated the hormonal control of PAI-1 gene expression and secretion in cultured human adipose tissue. We more particularly focused on the effects of glucocorticoids, insulin, cAMP, and catecholamines in explants from the omental region. The addition of dexamethasone to the culture medium increased PAI-1 secretion in a time-dependent manner for up to 24 h. The stimulation by the glucocorticoid was preceded by a 2-fold rise in PAI-1 messenger ribonucleic acid levels between 4-8 h of culture. The effectiveness of the glucocorticoid was concentration dependent, with a half-maximal effect within a physiological range. This stimulation was also observed in sc fat, but dexamethasone-stimulated as well as basal PAI-1 secretion rates were always higher in omental fat. Unlike dexamethasone, 24-h insulin did not modify PAI-1 secretion while accelerating glucose consumption. In contrast, 24-h cAMP inhibited PAI-1 gene expression and protein production under basal conditions and in the presence of dexamethasone. This inhibition was already detectable after 1 h and was maximal after 4 h at the level of gene expression. It occurred in both omental and sc adipose tissues. Importantly, epinephrine dose dependently inhibited PAI-1 parameters, an effect that was reproduced by isoproterenol. Dexamethasone- and cAMP-induced changes in PAI-1 messenger ribonucleic acid abundance were similar in explants and isolated fat cells. In isolated stromal-vascular cells, only dexamethasone was effective. In conclusion, we provide evidence for a reciprocal regulation of PAI-1 by dexamethasone (positive effector) and cAMP/catecholamines (negative effectors) in cultured human adipose tissue. The stimulation by glucocorticoids could contribute to enhanced production of PAI-1 by adipose tissue and high plasma levels of PAI-1 associated with central obesity and thereby be a link between this disorder and cardiovascular disease. Impaired inhibition by catecholamines could also contribute, as in vivo adipose tissue responses to these hormones are usually blunted in obese individuals.

Use of the circular stapler in 1000 consecutive colorectal anastomoses: experience of one surgical team.

BACKGROUND: This study was performed to assess the exact performance of the conventional way of stapling colorectal anastomoses. Information collected from 1000 consecutive anastomoses performed by one surgical team could be considered as reliable reference with which results obtained by new approaches could be compared. METHODS: One thousand consecutive anastomoses were performed from 1979 to 1992. Characteristics of the procedure, intraoperative events, mortality rate, complications, and clinical outcome were detailed. RESULTS: There were 528 men and 472 women (age range, 20 to 90 years; average age, 63 years). Anastomoses were constructed by means of a circular stapler loaded with the largest cartridge in 82.3% of the cases. Imperfections were identified during operation in 124 cases. A diverting colostomy was performed in 127 cases. Postoperative mortality rate averaged 2.2%. Clinical anastomotic leaks developed in 35 patients: in 11.4% after low stapling (less than 5 cm from the dentate line) and in 2.2% after high stapling. The presence of a diverting colostomy influenced the leakage rate in patients with very low anastomoses. Total failure rate (death, definitive colostomy) as a result of anastomotic leak was 1.6%. Among the 933 survivors who had follow-up examination, the incidence of bad functional results decreased from 10% at the first attendance to 4.3% at the last one. Transanal dilatation and restapling were required for symptomatic narrowing in three and one patients, respectively. CONCLUSIONS: The conventional way of stapling colorectal anastomoses in reliable, but it requires strict observance of the rules for anastomosing intestine and a careful check of the stapled sutures. Results obtained by new approaches could be compared with these data.

Surgery in Belgium.

To fully understand the present state of surgery in Belgium, it is necessary to know the structure of the Belgian State, the type of education, the statutory health insurance system, and the professional bodies representing surgeons. One of the most important problems is the excessive number of physicians, which recently led to the establishment of limits on the number of candidates receiving medical certification. Surgical training modalities are described and the results of a retrospective study concerning the quality of training are detailed. The continuing medical education and peer-review system (accreditation) is presented.

Idiopathic non-familial rectal and colonic varices requiring sigmoidorectal resection and coloanal anastomosis.

A 32-year-old male patient presenting with huge varices involving the sigmoid colon and the entire rectum down to the dentate line is described. There was no familial history of gastrointestinal bleeding. No particular aetiology was identified. Marked anaemia due to recurrent bleeding required resection of the sigmoid colon and rectum. Restoration of the intestinal continuity was performed by a coloanal anastomosis. The patient did well and bleeding has not recurred. To our knowledge, no similar case of such varices requiring extensive rectal surgery to control bleeding has been described in the literature.

MRI of the anal canal: correlation with histologic examination.

The purpose of this study was to correlate the MRI features of the anal canal with histologic findings. T1- and T2-weighted MR images of nine anal canals were obtained after fixation in 10% formalin. In three specimens, imaging was repeated after removal of histologic layers with a dissecting microscope. Corresponding histologic slices were stained with hematoxylin-eosin, Masson trichrome, and periodic acid-Schiff. Four layers were visualized on T2-weighted images. An inner layer of high signal intensity and a second layer of low signal intensity corresponded to the mucosa as well as mucous secretions and to the submucosa. The high signal intensity layer vanished at the distal part of the anal canal in accordance with the lack of mucus-secreting epithelium below the level of the dentate line. A third layer of intermediate signal intensity corresponded to the internal sphincter. A fourth layer of low signal intensity corresponded to the longitudinal muscle and external sphincter. T2-weighted MRI is capable of showing the internal architecture of the wall of the anal canal. In particular, the internal sphincter can be differentiated from the external sphincter and longitudinal muscle.

The use of prosthetic material in rectopexies.

Among the 80 different techniques that have been devised to repair rectal prolapse, abdominal rectopexies are the most suitable. The majority of these operations secure the rectum to the sacrum by means of a prosthetic material. Ripstein's technique, in USA, and Wells procedure, in Great Britain, have gained wide acceptance, despite a rather high rate of complications. A modified technique has been recently proposed by Keighley et al., with excellent results. From 1979 to 1982, 20 patients were operated upon in our department for rectal prolapse. The mean age of the patients was 43 years, and there was a rather high percentage of male patients (30%). Eleven exhibited an obvious external prolapse patients (30%). Eleven exhibited an obvious external prolapse but the others complained of the "occult rectal prolapse syndrome". The Orr-Loygue procedure, that secures the rectum to the sacral promontory by means of two strips of nylon mesh, was performed in all these cases. No mortality was observed and the morbidity was minimal. No infectious complications occurred. The procedure was performed without sexual consequences in the young patients. Clinical, endoscopic and cineradiographic checks illustrate that the Orr-Loygue rectopexy is an efficient treatment of both incipient intussusception and external prolapse, and offers good control of most associated troubles. But a longer survey is necessary before definitive conclusions may be drawn.

[Performance of endorectal echography in tumors of the rectum]. / Performance de l'échographie endorectale en pathologie tumorale du rectum.

From November 1986 to December 1987, endorectal ultrasound (EUS) has been performed 57 times in a total of 54 patients. In the cancers of the low and mid rectum (n = 34), the extent of the tumoral infiltration was accurately assessed by preoperative EUS in 88% of cases. Sensitivity of tumor spread beyond the rectal wall was 0.96. Classification of lymph nodes was more hazardous. The muscular layer was intact in 5 villous adenomas. The diagnosis was difficult in the case of a huge and massively secreting tumour. In the follow-up of the patients after rectal resection(n = 11) or local excision (n = 3) for cancer, EUS allowed an accurate analysis of the suture line in 12 cases. Three submucosal recurrences were detected. The follow-up showed no recurrence in the other cases with a tumor-free suture line pattern. The literature confirms that EUS is a non invasive, efficient and inexpensive method in the preoperative staging of non stenotic rectal tumors. The problem of accuracy of lymph node staging has not been resolved. The technique shows some promise in detecting local recurrences.

[Solitary lesions of the rectum caused by suppositories combining acetylsalicylic acid and paracetamol]. / Lésions solitaires du rectum dues à des suppositoires associant acide acétylsalicylique et paracétamol.

The reports of 8 female patients who, because of recurrent headache, were using analgesic suppositories containing acetylsalicylic acid and paracetamol (Perdolan) for more than two years are analyzed. Symptoms were nonspecific: anal pain, rectal tenesmus or bleeding. The lesions were located within 8 cm from the anal verge and consisted of superficial ulcerations, fibrotic scar tissue and rectal stenosis. Biopsies showed non-specific inflammation, limited to the rectum. Rectal prolapse or intussusception was not associated. By discontinuing the use of suppositories, symptoms usually resolved; rectal stenoses required anorectal dilatations and in 2 cases surgical resection. When solitary rectal lesions are observed in the absence of rectal prolapse, chemical aggression of the rectal mucosa by use of suppositories containing acetylsalicylic acid should be considered.

[Ileo-anal anastomosis in hemorrhagic-ulcerative rectocolitis and familial adenomatous polyposis: is it mandatory to perform resection of the endo-anal mucosa?]. / L'anastomose iléo-anale dans la rectocolite ulcéro-hémorragique et la polypose adénomateuse familiale: faut-il faire une mucosectomie endo-anale de principe?

The aim of this study was to assess the clinical outcome after ileal pouch-anal anastomosis with mucosectomy for ulcerative colitis and for familial adenomatous polyposis, and to characterize the histology of the stripped endoanal mucosa with particular reference to the ulcerative colitis activity, adenomatous polyps and dysplasia. Twenty-eight patients were operated, 16 for ulcerative colitis (group I) and 12 for familial adenomatous polyposis (group II). In group I, there were no intraoperative complications, but mucosectomy was tedious in 10 patients (62%) and the anastomosis was performed under some degree of tension in 10 patients (62%). In group II, there was a direct injury of the internal sphincter by a posterior tear during the mucosal stripping in one case. Mucosectomy was easy to perform in 8 patients (67%) and 10 anastomoses (84%) were performed under tension. In both groups, there were no postoperative complications related to the mucosectomy or to the anastomosis itself. Functional results were good, with a normal continence in 80% of ulcerative colitis patients and 92% of familial adenomatous polyposis patients. Review of histological sections of the stripped anal mucosa in group I showed chronic active ulcerative colitis in 8 patients (50%), chronic non-active ulcerative colitis in 4 (25%) and quiescent ulcerative colitis in 4 (25%). There was only one case of moderate dysplasia in a patient with a Dukes A carcinoma. In group II, anal mucosa showed micropolyps in all cases with mild dysplasia in 3 cases (25%) and moderate dysplasia in 9 (75%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Classification and diagnosis of anal fistulas]. / Classification et diagnostic des fistules anales.

Parks' classification of the anal fistulas is based on the knowledge of the pathogenesis of the disease. It relates fistula tracks to the anatomy of the anorectal musculature. Four main types are described, with some variations in each group: inter-, trans-, supra- and extrasphincteric fistulas. A circumferential spread occurs in the horseshoe fistulas. Positive diagnosis of fistula is difficult when the secondary opening lies distant from the anus. Aetiological factors, topography of the tracks, and clinical form (benign or necrotizing fasciitis) are systematically established. Anal fistulas must be differentiated from other suppurations of the anorectal area: intestinal (tumours, actinomycosis, piles,...) and extravisceral diseases (pilonidal cyst, hidradenitis suppurativa, bartholinitis...).

Primary melanosarcoma of the rectum.

We report two cases of anorectal malignant melanoma observed these last four years in the department. The first case was a 62-year-old female patient, and the second case was a 68-year-old male patient. Both suffered from a primary rectal tumour, arising from the rectum, with an intact anal canal. There were pulmonary metastases in the latter patient. At rectal biopsies, tumours were poorly differentiated and diagnosis of malignant melanoma could only be established by the complementary immuno-histochemical methods. The first patient had an AP excision of the rectum and died from generalized disease seven months later. In the second case, only palliative irradiation was carried out and the patient died six weeks later. Literature review confirms that rectal melanoma is a very rare tumour. Diagnosis is difficult, especially in the amelanotic forms. Prognosis remains very poor and the best therapeutic approach is still controversial.

[Radiological aspects of peri-diverticular disease of the colon. An anatomo-pathological correlation (author's transl]. / Aspects radiologiques de la péridiverticulite colique. Corréltaion avec l'anatomie pathologique.

Sixty consecutive cases operated for diverticular disease of the colon within the last 10 years are reviewed. A comparative study is made of the anatomopathological examination of the specimens and their radiological aspect trying to establish the precise radiological picture of acute, chronic and fibrotic peri-diverticular disease. Plain films of the abdomen, intravenous uro- and cystography are very useful in acute cases. A baryum enema just prior to surgery (33 cases) heralds by the rigid aspect of the involved bowelsegment the acute case; spasms, thick disorderly folds and localized extravasation characterize the acute peridiverticulitis. Fibrotic peri-diverticular disease shows disorderly, fine but "ragged" folds associated with extrinsic fistulae. In many cases the inflammation is not purely acute nor chronic or fibrotic. The distinguishing histological types are simultaneously present and render the radiological picture complex.

[Use of EEA stapler in colorectal surgery (author's transl)]. / Apport de l'agrafeuse EEA dans la chirurgie colo-rectale.

From March 1979 to January 1980, the EEA stapler was used in the construction of 46 anastomoses after left colonic and anterior rectal resections. The mortality was 0 and the morbidity minimal. The safety of the sutures was excellent. The operative procedure was greatly facilitated, mainly in the cases of low rectal anastomoses. The functional results were good. In the surgical treatment of the rectal carcinomas, the use of the EEA allowed larger margins of resection, and increased the rate of conservative operations [Acta chir. belg., 1981, 80, 11-15].

Early feeding after colorectal surgery. Preliminary results.

Thirty three patients were placed under early oral feeding after elective colorectal surgery. There were 15 male and 18 female patients, mean age: 52 years. Nasogastric tube was removed as soon as they were widely awake, or on the morning following the afternoon operations. Oral feeding was resumed 4 hours later, and the first meal consisted in a slight solid meal. There was no postoperative mortality or significant morbidity. Liquid and solid oral intakes were resumed 18 and 24 hours respectively after the operation. Tolerance was perfect in 22 patients (66%), good (slight complaints) in 16%, and was considered as fair or bad in the last six cases. Intestinal transit was observed after a median period of 2 days. Tube insertion rate was 12%. No adverse effect on the anastomoses was noted. Data from the literature confirm that early feeding is tolerable and safe after open colorectal surgery. More patients should be included in this protocol to take benefit of the physiological effects of early oral feeding.

[The surgical treatment of obstructive cancers of the left colon. Apropos of a series of 66 cases]. / Le traitement chirurgical des cancers occlusifs du côlon gauche. A propos d'une série de 66 cas.

From 1977 to 1989, 66 patients were operated on in emergency, without any bowel preparation, for acutely obstructing left-sided colon cancer. Two synchronous cancers were diagnosed and the 68 tumours were located as follows: 13 on the left transverse colon or at the splenic flexure, 7 on the descending colon, 37 on the sigmoid, and 11 at the rectosigmoid junction or below. According to Astler-Coller staging, 15 patients were classified as B, 17 as C and 25 as D. Initial treatment was a colostomy in 58 patients (88%), or a resection with or without anastomosis in 2 and 6 cases respectively. Most patients underwent a two- or more rarely a three-stage resection and 44 patients left the hospital without either tumour or stomy. Cumulative operative mortality was 12%. Five-year survival rates were 21% for the patients with a minimal potential follow-up of 5 years, and 39% for curative resections (disease-free survival of 33%). From these results, we think that two-staged resection, with close proximal colostomy followed by resection and anastomosis, remains an appropriate approach for most obstructing left-sided colon cancers; more tempting procedures such as resection with primary anastomosis or subtotal colectomy are probably indicated in selected patients.

[Liposarcoma of the ischiorectal fossa, an unusual tumoral site]. / Le liposarcome de la fosse ischiorectale, une localisation tumorale inhabituelle.

The main locations of the liposarcoma, the most common of the soft tissue sarcomas, are the lower limbs and the retroperitoneal space. We report the case of a 58 year-old male patient presenting with a huge and painless mass of the left fossa ischiorectalis. Preoperative tests and CT-scan of the pelvis evoked the diagnosis of liposarcoma, laminating and lifting the rectum and bladder. Visceral walls were respected. The patient underwent a en-bloc excision of the tumour by a combined perineal and abdominal route. Pathological examination of the mass (1.7 kg) confirmed the diagnosis of well differentiated liposarcoma. No further treatment was initiated, but, because of the high risk of local recurrence, the patient has been placed under a close follow-up schedule.

Subacute ischaemic proctitis: a rare condition requiring extensive rectal surgery.

Subacute ischaemic proctitis is a rare condition. We describe the case of a 60-year-old male patient who developed, after aortic aneurysm repair, a transient ischaemic colitis that totally healed without sequelae. He eventually developed symptoms of severe proctitis. Investigations identified a stenosis of the mid rectum, while the upper rectum was inflammatory. On angiogram, there was a poor blood flow through the Riolan's arcade and a stenosis of the proximal aorto-graft anastomosis. Diagnosis of subacute ischaemic proctitis due to poor blood supply through the internal iliac arteries was made. Anti-inflammatory drugs and dilations were inefficient. A subtotal proctectomy with low colorectal anastomosis was required. On pathological specimen, the lesions were strongly suggestive of an ischaemic process. The patient had an excellent recovery and was asymptomatic 8 months after the operation.

[Digestive fistulas in Crohn's disease]. / Fistules digestives dans la maladie de Crohn.

From 1977 up to 1983, 29 patients were operated upon for Crohn's disease with digestive fistula (dead fistulae, ileocecal and contiguous ileoileal fistulae being excluded). The majority of the fistulae arose from the distal ileum (n = 22). After an average duration of the disease of 7 1/2 years, the patients were admitted for surgical treatment, either electively (group I, n = 19), or in urgency (group II, n = 10). Eleven patients exhibited some signs of malnutrition, 13 needed a total parenteral nutrition for an average of 10 days; one patient had to be operated upon in emergency (hemorrhage and sepsis); the others had a normal bowel preparation. The resection of the diseased bowel at the origin of the fistulae included right ileocolic resections (n = 25), left (n = 1) or total (n = 3) colectomies, with primary anastomosis in all but two cases. The "target bowel" was treated as conservatively as possible: limited small bowel resection, single suture of the gastric, duodenal or sigmoidal walls, and bladder drainage. A segmental resection of the sigmoid colon was realized in 5 cases where a single closure of the wall defect was impossible. There was no postoperative death, no septic complications, and no signs of anastomotic dehiscence. Fistula recurrence "in situ" occurred only once. A spectacular health improvement, with a significant weight gain, was observed in 85% of the cases. Further outcome of the disease remains out of control.